Dataset Information

The impact of cruciferous vegetable isothiocyanates on histone acetylation and histone phosphorylation in bladder cancer.

ABSTRACT: Cruciferous vegetable intake is associated with reduced risk of bladder cancer, yet mechanisms remain unclear. Cruciferous vegetable isothiocyanates (ITCs), namely sulforaphane (SFN) and erucin (ECN), significantly inhibit histone deacetylase (HDAC) activity in human bladder cancer cells representing superficial to invasive biology (59-83% inhibition with 20μM, 48h treatment), and in bladder cancer xenografts (59±3% ECN inhibition). Individual HDACs inhibited by SFN and ECN include HDACs 1, 2, 4 and 6. Interestingly, global acetylation status of histones H3 or H4 remain unaltered. The interplay between HDAC inhibition and modest modulation of AcH3 and AcH4 status is partially explained by decreased histone acetyl transferase activity (48.8±5.3%). In contrast, a significant decrease in phosphorylation status of all isoforms of histone H1 was observed, concomitant with increased phosphatase PP1β and PP2A activity. Together, these findings suggest that ITCs modulate histone status via HDAC inhibition and phosphatase enhancement. This allows for reduced levels of histone H1 phosphorylation, a marker correlated with human bladder cancer progression. Therefore, ITC-mediated inhibition of histone H1 phosphorylation presents a novel direction of research in elucidating epidemiological relationships and supports future food-based prevention strategies.

Significance

Collectively, our findings suggest that the cruciferous vegetable isothiocyanates: sulforaphane (SFN) and erucin (ECN), impact histones status in bladder cancer cells by modulating specific HDACs and HATs, and enhancing phosphatase activity, resulting in reduction of histone H1 phosphorylation. These findings are significant due to the fact that our previous work positively correlated histone H1 phosphorylation with bladder cancer carcinogenesis and progression. Therefore, we propose that SFN and ECN may inhibit bladder carcinogenesis via epigenetic modulation of gene expression associated with histone H1 phosphorylation. These efforts may elucidate biomarkers useful in epidemiologic studies related to cruciferous vegetable intake and cancer risk or provide intermediate biomarkers for food-based clinical intervention studies in high-risk cohorts.

SUBMITTER: Abbaoui B

PROVIDER: S-EPMC5324139 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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The impact of cruciferous vegetable isothiocyanates on histone acetylation and histone phosphorylation in bladder cancer.

Abbaoui Besma B Telu Kelly H KH Lucas Christopher R CR Thomas-Ahner Jennifer M JM Schwartz Steven J SJ Clinton Steven K SK Freitas Michael A MA Mortazavi Amir A

Journal of proteomics 20170127

Cruciferous vegetable intake is associated with reduced risk of bladder cancer, yet mechanisms remain unclear. Cruciferous vegetable isothiocyanates (ITCs), namely sulforaphane (SFN) and erucin (ECN), significantly inhibit histone deacetylase (HDAC) activity in human bladder cancer cells representing superficial to invasive biology (59-83% inhibition with 20μM, 48h treatment), and in bladder cancer xenografts (59±3% ECN inhibition). Individual HDACs inhibited by SFN and ECN include HDACs 1, 2, 4 ...[more]

PMID: 28132875

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Project description:BackgroundPancreatic cancer is a deadly malignancy with limited screening and few modifiable risk factors. The objective of this study was to investigate the association between a modifiable lifestyle behavior, cruciferous vegetable consumption, and pancreatic cancer, both overall and by subgroups based on non-modifiable, established risk factors.MethodsWe conducted a hospital-based, case-control study utilizing data from the Patient Epidemiology Data System (1982-1998) at Roswell Park Comprehensive Cancer Center (Buffalo, NY) which included 183 pancreatic cancer patients and 732 cancer-free controls. Data were collected using a self-administered questionnaire including a 52-item food frequency questionnaire and other epidemiologic data. Multivariable logistic regression, adjusted for age, body mass index (BMI), sex, smoking status, total meat, and family history of pancreatic cancer, was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the associations between cruciferous vegetable consumption and pancreatic cancer. Subgroup analyses were conducted by sex, smoking status, and BMI.ResultsWe observed inverse associations between cruciferous vegetable intake and pancreatic cancer, with a significant 40% lower odds of pancreatic cancer among subjects consuming >1.5 servings per week (SPW) of raw cruciferous vegetables compared to those consuming less than 0.5 SPW (OR = 0.60, 95% CI: 0.39-0.93). Each additional SPW of total, raw, and cooked cruciferous vegetables was associated with a significant 7-15% lower odds of pancreatic cancer, with the strongest association seen in raw cruciferous vegetables (OR = 0.85, 95% CI: 0.75-0.95). We observed inverse associations between raw cruciferous vegetable intake and pancreatic cancer among people who were overweight, former smokers, and males, ranging from 50% to 59% lower odds.ConclusionConsuming cruciferous vegetables, especially raw cruciferous vegetables, is a modifiable lifestyle behavior which may be inversely associated with pancreatic cancer, including among subgroups with other non- or not easily modifiable risk factors for this deadly malignancy.

Project description:BackgroundBladder cancer is one of the top 10 most common cancers in the United States. Most bladder cancers (70%-80%) are diagnosed at early stages as non-muscle-invasive bladder cancer (NMIBC), which can be removed surgically. However, 50% to 80% of NMIBC cases recur within 5 years, and 15% to 30% progress with poor survival. Current treatments are limited and expensive. A wealth of preclinical and epidemiological evidence suggests that dietary isothiocyanates in cruciferous vegetables (Cruciferae) could be a novel, noninvasive, and cost-effective strategy to control NMIBC recurrence and progression.ObjectiveThe aim of this study is to develop a scalable dietary intervention that increases isothiocyanate exposure through Cruciferae intake in NMIBC survivors.MethodsWe worked with a community advisory board (N=8) to identify relevant factors, evidence-based behavior change techniques, and behavioral theory constructs used to increase Cruciferae intake in NMIBC survivors; use the PEN-3 Model focused on incorporating cultural factors salient to the group's shared experiences to review the intervention components (eg, the saliency of behavioral messages); administer the revised intervention to community partners for their feedback; and refine the intervention.ResultsWe developed a multicomponent intervention for NMIBC survivors consisting of a magazine, tracking book, live telephone call script, and interactive voice messages. Entitled POW-R Health: Power to Redefine Your Health, the intervention incorporated findings from our adaptation process to ensure saliency to NMIBC survivors.ConclusionsThis is the first evidence-based, theoretically grounded dietary intervention developed to reduce bladder cancer recurrence in NMIBC survivors using a systematic process for community adaptation. This study provides a model for others who aim to develop behavioral, community-relevant interventions for cancer prevention and control with the overall goal of wide-scale implementation and dissemination.

Project description:BackgroundHigh recurrence and progression rates are major clinical challenges for non-muscle-invasive bladder cancer (NMIBC). Dietary isothiocyanates (ITCs), phytochemicals primarily from cruciferous vegetables (CV), show strong anticancer activities in preclinical BC models, yet their effect on NMIBC prognosis remains unknown.ObjectivesThis study aimed to investigate the associations of dietary ITC exposure at diagnosis with NMIBC recurrence and progression.MethodsThe study analyzed 1143 participants from the Be-Well study, a prospective cohort of newly diagnosed NMIBC cases in 2015-2019 with no prior history of BC. Dietary ITC exposure was indicated by self-reported CV intake, estimated ITC intake, urinary metabolites, and plasma ITC-albumin adducts. Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for recurrence and progression, and unconditional logistic regression models were used to calculate odds ratios (ORs) and 95% CIs for delayed and multiple recurrence.ResultsOver a mean follow-up of 25 mo, 347 (30%) developed recurrence and 77 (6.7%) had disease progression. Despite no significant associations with the overall risk of recurrence, urinary ITC metabolites (OR: 1.96; 95% CI: 1.01, 4.43) and dietary ITC intake (OR: 2.13; 95% CI: 1.03, 4.50) were associated with late recurrence after 12-mo postdiagnosis compared with before 12-mo postdiagnosis. Raw CV intake was associated with reduced odds of having ≥2 recurrences compared with having one (OR: 0.34; 95% CI: 0.16, 0.68). Higher plasma concentrations of ITC-albumin adducts were associated with a reduced risk of progression, including progression to muscle-invasive disease (for benzyl ITC, HR: 0.40; 95% CI: 0.17, 0.93; for phenethyl ITC, HR: 0.40; 95% CI: 0.19, 0.86).ConclusionsOur findings indicate the possible beneficial role of dietary ITCs in NMIBC prognosis. Given the compelling preclinical evidence, increasing dietary ITC exposure with CV intake could be a promising strategy to attenuate recurrence and progression risks in patients with NMIBC.

Dataset Information

The impact of cruciferous vegetable isothiocyanates on histone acetylation and histone phosphorylation in bladder cancer.

Significance

Publications

The impact of cruciferous vegetable isothiocyanates on histone acetylation and histone phosphorylation in bladder cancer.

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